Streptolysin O (SLO; GAS25) is one of the most important virulence factors of the human pathogen Streptococcus pyogenes (GAS). Because of its capacity to invoke an early and strong immune response in humans, it is routinely used as a diagnostic marker of GAS infection.
SLO belongs to the family of the highly homologous thiol-activated cytolysins (TACYs), which exert their cytolytic activity through interaction with cholesterol on the cell membrane, self-oligomerization, and formation of pores. Furthermore, their capacity to activate directly the classical complement pathway by binding to the Fc region of human IgG may result in direct complement-mediated attack on host cells. TACYs can also interfere with host defense and immune cell function by means of the induction of cytokines and inflammatory mediators.
Some TACYs can passively and actively protect laboratory animals. See FEMS Lett. 182, 197-205, 2000. However, the use of these toxins as vaccine candidates has been hampered by their complex pattern of harmful side effects. There is, therefore, a need in the art for SLO proteins which are not toxic.